Apigenin: Difference between revisions

| Watchedfields = changed

| verifiedrevid = 443662850

| Name = Apigenin

| Reference =<ref>''[[Merck Index]]'', 11th Edition, '''763'''.</ref>

| ImageFile = Apigenin.svg

| ImageFile2 = Apigenin-3D-balls.png

| ImageSize =

| ImageName = Apigenin

| IUPACName = 4′,5,7-Trihydroxyflavone

| SystematicName = 5,7-Dihydroxy-2-(4-hydroxyphenyl)-4''H''-1-benzopyran-4-one

| OtherNames =Apigenine; Chamomile; Apigenol; Spigenin; Versulin; C.I. Natural Yellow 1

|Section1={{Chembox Identifiers

| IUPHAR_ligand = 4136

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| CASNo = 520-36-5

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 7V515PI7F6

| ChEBI_Ref = {{ebicite|correct|EBI}}

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| PubChem = 5280443

|Section2={{Chembox Properties

| Appearance = Yellow crystalline solid

| C=15 | H=10 | O=5

| MeltingPtC = 345 to 350

| MeltingPt_notes =

| LambdaMax = 267, 296sh, 336 nm in methanol<ref>The Systematic Identification of Flavonoids. Mabry et al, 1970, page 81</ref>

'''Apigenin''' (4′,5,7-trihydroxyflavone), found in many plants, is a [[natural product]] belonging to the [[flavone]] class that is the [[aglycone]] of several naturally occurring [[glycosides]]. It is a yellow crystalline solid that has been used to dye wool.

==Sources in nature==

Apigenin is found in many fruits and vegetables, but [[parsley]], [[celery]], [[celeriac]], and [[chamomile]] tea are the most common sources.<ref>[http://medicalxpress.com/news/2013-05-compound-mediterranean-diet-cancer-cells.html The compound in the Mediterranean diet that makes cancer cells 'mortal' ] Emily Caldwell, Medical Express, May 20, 2013.</ref> Apigenin is particularly abundant in the flowers of chamomile plants, constituting 68% of total [[flavonoid]]s.<ref name="pmid26487830">{{cite journal | vauthors = Venigalla M, Gyengesi E, Münch G | title = Curcumin and Apigenin – novel and promising therapeutics against chronic neuroinflammation in Alzheimer's disease | journal = Neural Regeneration Research | volume = 10 | issue = 8 | pages = 1181–5 | date = August 2015 | pmid = 26487830 | pmc = 4590215 | doi = 10.4103/1673-5374.162686 | doi-access = free }}</ref> Dried parsley can contain about 45&nbsp;[[Kilogram#SI multiples|mg]]&nbsp;apigenin/gram of the herb, and dried chamomile flower about 3–5&nbsp;mg/gram.<ref name="pmid29399439">{{cite journal | vauthors=Shankar E, Goel A, Gupta K, Gupta S | title=Plant flavone apigenin: An emerging anticancer agent | journal=[[Current Pharmacology Reports]] | volume=3 | issue=6 | pages=423–446 | year=2017 | doi = 10.1007/s40495-017-0113-2 | pmc=5791748 | pmid=29399439}}</ref> The apigenin content of fresh parsley is reportedly 215.5&nbsp;mg/100 grams, which is much higher than the next highest food source, green celery hearts providing 19.1&nbsp;mg/100 grams.<ref name="lpi-flav">{{cite web | last = Delage, PhD | first = Barbara | title = Flavonoids | url=http://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/flavonoids|publisher=[[Linus Pauling Institute]], Oregon State University | location=Corvallis, Oregon|access-date=2021-01-26|date=November 2015}}</ref>

== Pharmacology ==

Apigenin competitively binds to the benzodiazepine site on [[GABAA receptor|GABA_A]] receptors.<ref>{{Cite journal |last=Viola |first=H. |last2=Wasowski |first2=C. |last3=Levi de Stein |first3=M. |last4=Wolfman |first4=C. |last5=Silveira |first5=R. |last6=Dajas |first6=F. |last7=Medina |first7=J. H. |last8=Paladini |first8=A. C. |date=June 1995 |title=Apigenin, a component of Matricaria recutita flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects |url=https://pubmed.ncbi.nlm.nih.gov/7617761/ |journal=Planta Medica |volume=61 |issue=3 |pages=213–216 |doi=10.1055/s-2006-958058 |issn=0032-0943 |pmid=7617761}}</ref> There exist conflicting findings regarding how apigenin interacts with this site.<ref>{{Cite journal |last=Dekermendjian |first=K. |last2=Kahnberg |first2=P. |last3=Witt |first3=M. R. |last4=Sterner |first4=O. |last5=Nielsen |first5=M. |last6=Liljefors |first6=T. |date=1999-10-21 |title=Structure-activity relationships and molecular modeling analysis of flavonoids binding to the benzodiazepine site of the rat brain GABA(A) receptor complex |url=https://pubmed.ncbi.nlm.nih.gov/10543878/ |journal=Journal of Medicinal Chemistry |volume=42 |issue=21 |pages=4343–4350 |doi=10.1021/jm991010h |issn=0022-2623 |pmid=10543878}}</ref><ref>{{Cite journal |last=Avallone |first=R. |last2=Zanoli |first2=P. |last3=Puia |first3=G. |last4=Kleinschnitz |first4=M. |last5=Schreier |first5=P. |last6=Baraldi |first6=M. |date=2000-06-01 |title=Pharmacological profile of apigenin, a flavonoid isolated from Matricaria chamomilla |url=https://pubmed.ncbi.nlm.nih.gov/10751547/ |journal=Biochemical Pharmacology |volume=59 |issue=11 |pages=1387–1394 |doi=10.1016/s0006-2952(00)00264-1 |issn=0006-2952 |pmid=10751547}}</ref>

== Biosynthesis ==

Apigenin is biosynthetically derived from the general [[Phenylpropanoids metabolism|phenylpropanoid pathway]] and the flavone synthesis pathway.<ref>{{Cite journal|last=Forkmann|first=G.|date=January 1991|title=Flavonoids as Flower Pigments: The Formation of the Natural Spectrum and its Extension by Genetic Engineering|journal=Plant Breeding|language=en|volume=106|issue=1|pages=1–26|doi=10.1111/j.1439-0523.1991.tb00474.x|issn=0179-9541|doi-access=free}}</ref> The phenylpropanoid pathway starts from the aromatic amino acids L-phenylalanine or L-tyrosine, both products of the [[Shikimate pathway]].<ref>{{cite journal | vauthors = Herrmann KM | title = The shikimate pathway as an entry to aromatic secondary metabolism | journal = Plant Physiology | volume = 107 | issue = 1 | pages = 7–12 | date = January 1995 | pmid = 7870841 | pmc = 161158 | doi = 10.1104/pp.107.1.7 }}</ref> When starting from L-phenylalanine, first the amino acid is non-oxidatively deaminated by [[Phenylalanine ammonia-lyase|phenylalanine ammonia lyase]] (PAL) to make cinnamate, followed by oxidation at the ''para'' position by [[Trans-cinnamate 4-monooxygenase|cinnamate 4-hydroxylase]] (C4H) to produce ''p''-coumarate. As L-tyrosine is already oxidized at the ''para'' position, it skips this oxidation and is simply deaminated by [[Tyrosine ammonia-lyase|tyrosine ammonia lyase]] (TAL) to arrive at ''p''-coumarate.<ref>{{cite journal | vauthors = Lee H, Kim BG, Kim M, Ahn JH | title = Biosynthesis of Two Flavones, Apigenin and Genkwanin, in Escherichia coli | journal = Journal of Microbiology and Biotechnology | volume = 25 | issue = 9 | pages = 1442–8 | date = September 2015 | pmid = 25975614 | doi = 10.4014/jmb.1503.03011 | doi-access = free }}</ref> To complete the general phenylpropanoid pathway, [[4-Coumarate-CoA ligase|4-coumarate CoA ligase]] (4CL) substitutes coenzyme A (CoA) at the carboxy group of ''p''-coumarate. Entering the flavone synthesis pathway, the type III [[polyketide synthase]] enzyme [[chalcone synthase]] (CHS) uses consecutive condensations of three equivalents of [[Malonyl-CoA|malonyl CoA]] followed by aromatization to convert ''p''-coumaroyl-CoA to [[chalcone]].<ref>{{cite journal | vauthors = Austin MB, Noel JP | title = The chalcone synthase superfamily of type III polyketide synthases | journal = Natural Product Reports | volume = 20 | issue = 1 | pages = 79–110 | date = February 2003 | pmid = 12636085 | doi = 10.1039/b100917f | citeseerx = 10.1.1.131.8158 }}</ref> [[Chalcone isomerase]] (CHI) then isomerizes the product to close the pyrone ring to make [[naringenin]]. Finally, a flavanone synthase (FNS) enzyme oxidizes naringenin to apigenin.<ref>{{cite journal | vauthors = Martens S, Forkmann G, Matern U, Lukacin R | title = Cloning of parsley flavone synthase I | journal = Phytochemistry | volume = 58 | issue = 1 | pages = 43–6 | date = September 2001 | pmid = 11524111 | doi = 10.1016/S0031-9422(01)00191-1 }}</ref> Two types of FNS have previously been described; FNS I, a soluble enzyme that uses 2-oxogluturate, Fe²⁺, and ascorbate as cofactors and FNS II, a membrane bound, NADPH dependent cytochrome p450 monooxygenase.<ref>{{cite journal | vauthors = Leonard E, Yan Y, Lim KH, Koffas MA | title = Investigation of two distinct flavone synthases for plant-specific flavone biosynthesis in Saccharomyces cerevisiae | journal = Applied and Environmental Microbiology | volume = 71 | issue = 12 | pages = 8241–8 | date = December 2005 | pmid = 16332809 | pmc = 1317445 | doi = 10.1128/AEM.71.12.8241-8248.2005 | bibcode = 2005ApEnM..71.8241L }}</ref>

== Glycosides ==

The naturally occurring [[glycoside]]s formed by the combination of apigenin with sugars include:

* [[Apiin]] (apigenin 7-''O''-apioglucoside), isolated from [[parsley]]<ref>{{cite journal | vauthors = Meyer H, Bolarinwa A, Wolfram G, Linseisen J | title = Bioavailability of apigenin from apiin-rich parsley in humans | journal = Annals of Nutrition & Metabolism | volume = 50 | issue = 3 | pages = 167–72 | year = 2006 | pmid = 16407641 | doi = 10.1159/000090736 | s2cid = 8223136 | url = https://nbn-resolving.org/urn:nbn:de:bvb:384-opus4-857673 }}</ref> and celery

* [[Apigetrin]] (apigenin 7-[[glucoside]]), found in [[dandelion coffee]]

* [[Vitexin]] (apigenin 8-''C''-glucoside)

* [[Isovitexin]] (apigenin 6-''C''-glucoside)

* [[Rhoifolin]] (apigenin 7-''O''-[[neohesperidoside]])

* [[Schaftoside]] (apigenin 6-''C''-glucoside 8-''C''-[[arabinoside]])

==In diet==

Some foods contain relatively high amounts of apigenin:<ref name="Ref_USDA">[https://www.ars.usda.gov/ARSUserFiles/80400525/Data/Flav/Flav_R03.pdf USDA Database for the Flavonoid Content of Selected Foods, Release 3 (2011)]</ref>

{| class="wikitable"

|-

! Product

! Apigenin<br /><small>(milligrams per 100 grams)</small>

|-

|Dried parsley

|4500<ref name="pmid29399439" />

|-

| [[Chamomile]]

| 300–500

|-

| [[Parsley]]

| 215.5

|-

| [[Celery hearts, green]]

| 19.1

|-

| [[Rutabaga|Rutabagas, raw]]

| 4

|-

|

|}

== See also ==

* [[Amentoflavone]]

== References ==

{{Reflist|32em}}

{{Phytoestrogens}}

{{Adenosinergics}}

{{Estrogenics}}

{{GABAAR PAMs}}

{{Glutamatergics}}

{{Opioidergics}}

{{Progestogenics}}

[[Category:Aromatase inhibitors]]

[[Category:Delta-opioid receptor antagonists]]

[[Category:GABAA receptor positive allosteric modulators]]

[[Category:Kappa-opioid receptor antagonists]]

[[Category:Mu-opioid receptor antagonists]]

[[Category:NMDA receptor antagonists]]

[[Category:Phytoestrogens]]

[[Category:Progestogens]]